There is a rationale for further evaluating the role of mycoplasmas in the human rheumatic diseases; this rationale is based on (i) the established role of mycoplasmas as etiological agents of several animal arthritides; (ii) accumulating evidence associating the human mycoplasmal flora with aspects of inflammatory rheumatic diseases; and (iii) recent evidence describing mutational systems driving adaptive surface variation of human mycoplasma species. This project focuses on characterizing the interaction of human mycoplasmas with their host, with specific emphasis on individuals with defined rheumatic disorders. To further delineate a possible role of mycoplasmas in these diseases, it is specifically proposed to: 1) examine disease sites by selective PCR to detect, classify, and characterize mycoplasmas associated with pathologic lesions; 2) characterize a newly identified and highly individual B cell response to select subsets of epitope repertoires displayed on variant surface membrane lipoproteins of human mycoplasmas; and 3) define the molecular basis of surface lipoprotein variation in these mycoplasma species. Techniques include PCR amplification and analysis of target sequences in host-derived materials, immunologic screening protocols to define patterns of serologic reactivities, and characterization of membrane protein genes by transposon mutagenesis and standard molecular techniques. It is anticipated that information emerging from these studies will directly contribute to an understanding of the nature of mycoplasma infections, their association with the rheumatic diseases, the mechanism of pathogenesis, methods for detection, and formulation of strategies to control these chronic disorders.